patoloji-ders-notlari

Title

Serdar Balcı

Harvey Williams Cushing

first anaesthetic chart

clinical use of X-rays

relationship between systolic blood pressure and cranial pressure

application of electrical coagulation to neurosurgery

https://en.wikipedia.org/wiki/Harvey_Cushing

http://www.whonamedit.com/doctor.cfm/980.html

Ann R Coll Surg Engl. 1969 Apr;44(4):180-1.

Ann Surg. 1909 Dec;50(6):1002-17.

Ann Surg. 1909 Dec;50(6):1002-17.

Pituitary. 2010 Dec;13(4):324-8.

Pituitary. 2010 Dec;13(4):324-8.

Pituitary. 2010 Dec;13(4):324-8.

Pituitary. 2010 Dec;13(4):324-8.

Pituitary. 2010 Dec;13(4):324-8.

Pituitary. 2010 Dec;13(4):324-8.

Pituitary. 2010 Dec;13(4):324-8.

Pituitary. 2010 Dec;13(4):324-8.

Davut’un Golyat’ı Öldürmesi (I.Samuel)

1.Sa.17: 4 Filist ordugahından Gatlı Golyat adında usta bir dövüşçüortaya çıktı. ** **Boyu ** **altı arşın bir karıştı*fe*.D Not 17:4 “Altı arşın bir karış”: ** **Yaklaşık 2.9 m .

1.Sa.17: 5 Başına tunç* miğfer takmış, pullu bir zırh kuşanmıştı. ** **Tunç zırhın ağırlığı __ beş bin şekeldi*ff*.D Not 17:5 “Beş bin şekel”: __ Yaklaşık 57.5 kg .

1.Sa.17: 6 Baldırları zırhlarla korunmuştu. Omuzları arasında tunç bir pala asılıydı.

1.Sa.17: 7 Mızrağının sapı dokumacı tezgahının sırığı gibiydi. ** **Mızrağındemir başının ağırlığı __ altı yüz şekeldi*fg*. Golyat’ın önüsıra kalkanını taşıyan bir adam yürüyordu.D Not 17:7 “Altı yüz şekel”: __ Yaklaşık 6.9 kg .

1.Sa.17: 8 Golyat durup İsrail ordusuna, “Neden savaş düzeni aldınız?” diye haykırdı, “Ben Filistli’yim, sizse Saul’un kölelerisiniz. Aranızdan karşıma çıkacak birini seçin.

1.Sa.17: 38 Sonra kendi giysilerini Davut’a verdi; başına tunç miğfer taktı, ona bir zırh giydirdi.

1.Sa.17: 39 Davut giysilerinin üzerine kılıcını kuşanıp yürümeye çalıştı. Çünkü bu giysilere alışık değildi. Saul’a, “Bunlarla yürüyemiyorum” dedi, “Çünkü alışık değilim.” Sonra giysileri üzerinden çıkardı.

1.Sa.17: 40 Değneğini alıp dereden beş çakıl taşı seçti. Bunları çoban dağarcığının cebine koyduktan sonra ** **sapanını alıp Filistli Golyat’a doğru ilerledi .

1.Sa.17: 48 Golyat saldırmak amacıyla Davut’a doğru ilerledi. Davut daonunla dövüşmek üzere hemen Filist cephesine doğru koştu.

1.Sa.17: 49 ** **Elini dağarcığına sokup bir taş çıkardı, sapanla fırlattı.Taş Filistli’nin alnına çarpıp saplandı. Filistli yüzükoyun yere düştü.

1.Sa.17: 50 Böylece Davut Filistli Golyat’ı sapan ve taşla yendi.Elinde kılıç olmaksızın onu yere serdi.

1.Sa.17: 51 Sonra koşup üzerine çıktı. Golyat’ın kılıcını tutupkınından çektiği gibi onu öldürdü ve başını kesti.Kahraman Golyat’ın öldüğünü gören Filistliler kaçtılar.

**Pierre Puget ‘David, vainqueur de Goliath’ **

*A History of Acromegaly * Pituitary 1999;2:7–28

Undoubtedly Goliath’s great size was due to ** **acromegaly ** **secondary to a pituitary macroadenoma. This pituitary adenoma was apparently large enough to induce ** **visual field deficits __ by its pressure on the optic chiasm, which made Goliath __ unable to follow the young David ** **as he circled him. The ** **stone entered Goliath’s cranial vault ** **through a ** **markedly thinned frontal bone , which resulted from enlargement of the frontal paranasal sinus, a frequent feature of acromegaly. The stone lodged in Goliath’s enlarged pituitary and caused a ** **pituitary hemorrhage , resulting in ** **transtentorial herniation and death .

**Radiology. 1990 Jul;176(1):288. **

Pituitary Diseases

Serdar BALCI, MD

Pituitary gland

• **small, bean-shaped **
• lies at the base of the brain within the sella turcica
• Related to the hypothalamus
  • stalk, composed of axons
  • venous plexus
• Anterior lobe (adenohypophysis)
• Posterior lobe (neurohypophysis)

Anterior pituitary (adenohypophysis)

• Epithelial cells
• Embryologically from the developing oral cavity
• Normal histology:
  • Cells containing basophilic cytoplasm
  • Eosinophilic cytoplasm
  • Poorly staining ( chromophobic ) cytoplasm

Robbins Basic Pathology

Robbins Basic Pathology

Pituitary Diseases

• Hyperpituitarism
  • excessive secretion of trophic hormones
  • Anterior pituitary adenoma
• Hypopituitarism

  • Deficiency of trophic hormones

  • Ischemic injury, surgery or radiation, and inflammatory reactions

  • Nonfunctional pituitary adenomas destruct normal structures

  • Local mass effects

  • Sellar expansion, bony erosion, and disruption of the diaphragma sellae

  • Compress decussating fibers in the optic chiasm

    • lateral (temporal) visual fields, bitemporal hemianopsia

  • Elevated intracranial pressure

    • headache, nausea, and vomiting

  • Extend into the base of the brain

    • invasive pituitary adenoma
    • seizures or obstructive hydrocephalus
    • cranial nerve palsy

  • Acute hemorrhage into an adenoma

    • rapid enlargement of the lesion
    • pituitary apoplexy
    • rapidly fatal

Hyperpituitarism

• The most common cause of hyperpituitarism is an adenoma arising in the anterior lobe
• Less common causes
  • Hyperplasia
  • carcinomas of the anterior pituitary
  • secretion of hormones by some extrapituitary tumors
  • Certain hypothalamic disorders

Pathogenesis of Pituitary Adenomas

• Guanine nucleotide–binding protein (G protein) mutations
• critical role in signal transduction
  • from cell surface receptors (e.g., growth hormone–releasing hormone receptor) to intracellular effectors (e.g., adenyl cyclase)
    • generate second messengers (e.g., cAMP).
  • encoded by the GNAS1 gene
• 40% of growth hormone–secreting somatotroph cell adenomas and a minority of adrenocorticotropic hormone (ACTH)–secreting corticotroph cell adenomas have GNAS1 mutations

• Familial pituitary adenomas
  • MEN1, CDKN1B, PRKAR1A, and AIP
  • Germline inactivating mutations of the MEN1 gene
    • multiple endocrine neoplasia syndrome type 1 (MEN-1)
  • CDKN1B gene
    • cell cycle checkpoint regulator p27 or KIP1
  • Germline mutations of CDKN1B
    • “MEN-1 like” syndrome who lack MEN1 abnormalities
  • Aryl hydrocarbon receptor–interacting protein (AIP)
    • pituitary adenoma predisposition gene
    • GH-secreting adenomas at a younger age (before 35 years) than that typical for sporadic GH adenoma patients
• Mutations of TP53
  • associated with a propensity for aggressive behavior, such as invasion and recurrence

Autopsy Pathology: A Manual and Atlas

Macroadenomas >1 cm

Microadenomas <1 cm

Robbins Basic Pathology

Pituitary adenoma is a well-circumscribed, soft lesion

Smaller tumors, be confined by the sella turcica

Larger lesions may compress the optic chiasm and adjacent structures

Erode the sella turcica and anterior clinoid processes

Extend locally into the cavernous and sphenoidal sinuses

30% of cases, nonencapsulated and infiltrate adjacent bone, dura, and (uncommonly) brain

Foci of hemorrhage and/or necrosis are common in larger adenomas

Robbins Basic Pathology

Massive, nonfunctioning adenoma has grown far beyond the confines of the sella turcica and has distorted the overlying brain

Nonfunctioning adenomas tend to be larger at the time of diagnosis than those that secrete a hormone

Robbins Basic Pathology

Relatively uniform, polygonal cells arrayed in sheets, cords, or papillae

Supporting connective tissue, or reticulin, is sparse

Soft, gelatinous consistency

Nuclei of the neoplastic cells may be uniform or pleomorphic

Mitotic activity usually is scanty

Cytoplasm of the constituent cells may be acidophilic, basophilic, or chromophobic, depending on the type and amount of secretory product within the cell, but it is fairly uniform throughout the neoplasm

Robbins Basic Pathology

anterior pituitary parenchyma

pituitary adenoma

Cellular monomorphism and the absence of a significant reticulin network distinguish pituitary adenomas from non-neoplastic anterior pituitary parenchyma

Pituitary Adenomas

• The functional status of the adenoma cannot be reliably predicted from its histologic appearance
• Adenomas with TP53 mutations
  • brisk mitotic activity
  • higher proliferation rates
  • Designated as “atypical adenomas”
  • potential for aggressive behavior
• Composed of a single cell type and produce a single predominant hormone
• Some pituitary adenomas can secrete two different hormones
  • growth hormone and prolactin most common combination
  • rarely plurihormonal
• Functional
  • Associated with hormone excess and clinical manifestations
• Nonfunctioning adenomas
  • Mass effects, hypopituitarism
  • Demonstration of hormone production at the tissue level only, without clinical manifestations of hormone excess
• Truly “hormone negative”
  • Absence of immunohistochemical reactivity or ultrastructural evidence of hormone production
• Nonfunctioning and hormone-negative adenomas
  • come to clinical attention at a later stage
  • Macroadenomas
  • may cause hypopituitarism

Pituitary Adenomas

Robbins Basic Pathology

Prolactinomas

Most common type of hyperfunctioning pituitary adenoma

Range in size from small microadenomas to large, expansile tumors associated with considerable mass effect

Prolactin is demonstrable within the cytoplasm of the neoplastic cells by immunohistochemical techniques

Hyperprolactinemia

• amenorrhea, galactorrhea, loss of libido, and infertility
• Diagnosed at an earlier stage in women of reproductive age
• May be quite subtle in men and older women
  • tumor may reach considerable size before coming to clinical attention
• Causes other than prolactin-secreting pituitary adenomas:
  • pregnancy
  • high-dose estrogen therapy
  • renal failure
  • hypothyroidism
  • hypothalamic lesions
  • dopamine-inhibiting drugs (e.g., reserpine)
  • Stalk effect
    • Any mass in the suprasellar compartment may disturb the normal inhibitory influence of hypothalamus on prolactin secretion, resulting in hyperprolactinemia
    • Mild elevations of serum prolactin (less than 200 µg/L) in a patient with a pituitary adenoma do not necessarily indicate a prolactin-secreting neoplasm

Robbins and Cotran Pathologic Basis of Disease

Growth Hormone–Producing (Somatotroph Cell) Adenomas

• Second most common type of functional pituitary adenoma

  • GH adenomas
  • Mixed GH+ PRL adenomas

• Clinical manifestations of excessive growth hormone may be subtle

• Somatotroph cell adenomas may be quite large by the time they come to clinical attention

• Composed of densely or sparsely granulated cells

• Immunohistochemical staining demonstrates growth hormone within the cytoplasm of the neoplastic cells

• Small amounts of immunoreactive prolactin often are present as well

• Persistent hypersecretion of growth hormone

  • Stimulates the hepatic secretion of insulin-like growth factor I (somatomedin C)
  • Causes many of the clinical manifestations

• Before the epiphyses close, prepubertal children

  • Gigantism
    • generalized increase in body size
    • disproportionately long arms and legs

• After closure of the epiphyses

  • Acromegaly
    • Growth in soft tissues, skin, and viscera and in the bones of the face, hands, and feet
    • Prognathism
      • Enlargement of the jaw results in its protrusion
      • Broadening of the lower face and separation of the teeth
    • Hands and feet are enlarged
    • Broad, sausage-like fingers

• Growth hormone excess

  • abnormal glucose tolerance
  • diabetes mellitus
  • generalized muscle weakness
  • hypertension
  • arthritis
  • osteoporosis
  • congestive heart failure

Adrenocorticotropic Hormone–Producing (Corticotroph Cell) Adenomas

• Most are small (microadenomas) at the time of diagnosis

• Stain positively with periodic acid–Schiff (PAS) stains

  • accumulation of glycosylated ACTH protein

• Secretory granules can be detected by immunohistochemical methods

• Electron microscopy they appear as membrane-bound, electron-dense granules averaging 300 nm in diameter

• May be clinically silent

• May cause hypercortisolism

  • Cushing syndrome
  • stimulatory effect of ACTH on the adrenal cortex

• Cushing disease

  • When the hypercortisolism is caused by excessive production of ACTH by the pituitary

• Nelson syndrome

  • Large, clinically aggressive corticotroph cell adenomas may develop after surgical removal of the adrenal glands for treatment of Cushing syndrome
  • when adrenals removed surgically
  • loss of the inhibitory effect of adrenal corticosteroids on a preexisting corticotroph microadenoma
  • patients present with the mass effects of the pituitary tumor

Gonadotroph (luteinizing hormone LH–producing and follicle-stimulating hormone FSH–producing) adenomas

Difficult to recognize

Secrete hormones inefficiently and variably

Secretory products usually do not cause a recognizable clinical syndrome

Detected with mass effects

Immunoreactivity for the common gonadotropin α-subunit and the specific β-FSH and β-LH subunits; FSH usually is the predominant secreted hormone

Thyrotroph (thyroid-stimulating hormone TSH–producing) adenomas

1% of all pituitary adenomas and constitute a rare cause of hyperthyroidism

Nonfunctioning pituitary adenomas

• 25% of all pituitary tumors
• Characterized by mass effects
• Hypopituitarism
• Clinically silent counterparts of the functioning adenomas
  • silent gonadotroph adenoma
• True hormone-negative (null cell) adenomas
  • infrequent

Pituitary carcinomas

Exceedingly rare

Local extension beyond the sella turcica

Distant metastases

Hypopituitarism

Loss or absence of 75% or more of the anterior pituitary parenchyma

Congenital (exceedingly rare)

Nonfunctioning pituitary adenomas

• Ischemic necrosis of the anterior pituitary

  • Sheehan syndrome
    • postpartum necrosis of the anterior pituitary
    • physiologic enlargement of the gland during pregnancy is not accompanied by an increase in blood supply from the low-pressure portal venous system
    • significant hemorrhage and hypotension during the peripartal period
    • posterior pituitary is not effected, receives its blood directly from arterial branches
  • disseminated intravascular coagulation
  • sickle cell anemia
  • elevated intracranial pressure
  • traumatic injury
  • shock of any origin

• The residual gland is shrunken and scarred

• Ablation of the pituitary by surgery or irradiation

• Inflammatory lesions

  • sarcoidosis or tuberculosis

• Trauma

• Metastatic neoplasms involving the pituitary

Clinical manifestations of anterior pituitary hypofunction

• Depend on the specific hormones that are lacking
• Growth hormone deficiency
  • Growth failure (pituitary dwarfism)
• Gonadotropin or gonadotropin-releasing hormone (GnRH) deficiency
  • amenorrhea and infertility in women
  • decreased libido, impotence, and loss of pubic and axillary hair in men
• TSH
  • hypothyroidism
• ACTH
  • hypoadrenalism
• Prolactin deficiency
  • failure of postpartum lactation
• Loss of stimulatory effects of MSH on melanocytes
  • Pallor

POSTERIOR PITUITARY SYNDROMES

Posterior Pituitary Syndromes

• Neurohypophysis
  • composed of modified glial cells (termed pituicytes )
  • Axonal processes extending from nerve cell bodies in the supraoptic and paraventricular nuclei of the hypothalamus
• Hypothalamic neurons produce two peptides
  • antidiuretic hormone (ADH) and oxytocin
  • They are stored in axon terminals in the neurohypophysis
  • Released into the circulation in response to stimuli
• Oxytocin
  • stimulates the contraction of smooth muscle in the pregnant uterus
  • muscle surrounding the lactiferous ducts of the mammary glands
  • Impairment of oxytocin synthesis and release has not been associated with significant clinical abnormalities
• ADH
  • diabetes insipidus
  • secretion of inappropriately high levels of ADH

Antidiuretic hormone

• Synthesized predominantly in the supraoptic nucleus
• ADH is released in response to
  • Increased plasma oncotic pressure, left atrial distention, exercise, and certain emotional states
  • acts on the collecting tubules of the kidney to promote the resorption of free water
• ADH deficiency causes diabetes insipidus

  • excessive urination (polyuria)

  • inability of the kidney to properly resorb water from the urine

  • Syndrome of inappropriate ADH (SIADH) secretion

    • Resorption of excessive amounts of free water
    • Hyponatremia, cerebral edema, neurologic dysfunction

  • ADH excess is caused by several extracranial and intracranial disorders

    • secretion of ectopic ADH by malignant neoplasms
      • small cell carcinomas of the lung
    • non-neoplastic diseases of the lung
    • Local injury to the hypothalamus or neurohypophysis

HYPOTHALAMIC SUPRASELLAR TUMORS

Craniopharyngioma

Autopsy Pathology: A Manual and Atlas

Craniopharyngioma

• Arise from vestigial remnants of Rathke pouch

• 1-5% of intracranial tumors

• Most are suprasellar, with or without intrasellar extension

• Bimodal age distribution

  • one peak in childhood (5 to 15 years)
  • second peak in adults 65 years or older

• Abnormalities of the WNT signaling pathway, mutations of β-catenin

• Average 3-4 cm in diameter

• Cystic and sometimes multiloculated

• Adamantinomatous craniopharyngioma

  • Children
  • Calcifications
  • cysts of adamantinomatous craniopharyngiomas often contain a cholesterol-rich, thick brownish-yellow fluid, “machine oil”

• Papillary craniopharyngioma

  • most often observed in adults

Robbins and Cotran Pathologic Basis of Disease

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Hipofiz adenomuna yaklaşım

Dr. Serdar Balcı

Klinik bilgi

• Çocuklarda: PRL, ACTH
• Hormon düzeylerinde artış
  • Hiperprolaktinemi → nonspesifik
• Kitle etkisi
  • Başağrısı
  • Görme alanı
  • Hipopituitarism
• D. insipid ve kraniel sinir arazı
  • Öncelikle diğer tümörler, metastazlar
  • İnflamatuar süreçler

Ameliyat

Eğer hemen patolojiye gelecekse SF içeren tüpte gönderilebilir. (Otoliz, formolsüz diye not konan rapor sayısı)

Gazlı bezi unutun

Formaldehit

EM inceleme?

Hipofiz adenomu - Frozen

• Doku genelde küçük
  • Donma artefaktı
• Yayma
  • Daha az doku yeterli
  • Deneyim gerektiriyor
• Tek tanısal materyal frozenda ** *harcanmış * **olabilir
• Frozen beklenmedik bir bulgu ile karşılaşınca uygulanabilir (başka tümör şüphesi)
• İntraoperatif retikülin?
• Cerrahi sınır?

Mikroadenom – Frozen?

Adenohipofiz

Lobüler yapı

Coğrafi dağılım

Tükrük bezi benzeri bezler gibi taklitçiler

Ara lob???

Nörohipofiz

Suprasellar kitleler - Ddx

Pituisitom

Lenfositik/granülamatöz hipofizit

Lenfoma

Gangliositom/Gangliositoadenom

Germ hücreli tümörler

Granüler hücrrli tümör

Plazmasitom

Lenfoma

Paragangliom

Metastaz

#

Sellar kitleler

Kraniyofarengiom

Rathke kleft kisti

Teratom

Kordoma

Germinom

Pilositik astrositom

Lenfoma

İnflamasyon

Langerhans hücreli histiyositoz

Granüler hücreli tümör

Glezer et al, Rare Sellar Lesions, Endocrinol Metab Clin N Am 37 (2008) 195–211

#

**Postmortem prevalence of pituitary adenoma is 14.4% **

radiologic studies identify a lesion consistent with pituitary adenoma in 22.2% of the population

providing an overall estimated prevalence of 16.9%.

Adenom - Hiperplazi

• Diffüz, nodüler
• Hiperplazi
  • Stimulus kesilince büyüme durur
  • Gebelik: laktotrop hücre proliferasyonu
  • Primer hipopituitarizm: tirotrop
  • Hipotalamik gangliositom, GHrH eksprese eden tümörler: somatotrop
  • __ CrH: bronşial, gastroenterohepatik, adrenal, prostat endokrin tümörler__

Hipofiz adenomu

FFPE – H&E

• H&E
• 10 boyasız
  • Retikülin
  • PAS?
  • MIB-1
  • p53
  • Hormonlar

Nükleus

Nükleol

Kromatin

Atipi?

Mitoz

Sitoplazma

Yapı

Papiller

Amiloid

Kalsifikasyon

Tedavi etkisi

Retikülin: Adenohipofiz, Hiperplazi, Adenom

Hormon belirteçleri

GH

GH – CK8

Prolaktin

Prolaktin – CK8

TSH

FSH

LH

ACTH

ACTH - mikroadenom

Retikülin ve ACTH IHK’sı gerekli

Yoğun granüllü

Bazofilik hücreler

PAS +

CAM 5.2, CK7, CK8

ACTH- Crooke değişiklik

• Tümörsüz alanda (genellikle kortikotroplarda)
• Dolaşımdaki artmış glukokortikoid varlığını yansıtır
  • Pituiter kortikotrop adenom
  • Ektopik ACTH sekresyonu
  • Primer adrenal patolojiler
  • İatrojenik
• Adenom görülmediyse mikroadenom varlığı araştırılmalı (1-2 mm’lik seri kesitler, retikülin ve ACTH ile bakılarak)
• Adenom görülmezse klinikopatolojik korelasyon gerektirir

ACTH- Crooke cell

• Adenom görülmediyse mikroadenom varlığı araştırılmalı
  • 1-2 mm’lik seri kesitler
  • Retikülin ve ACTH ile bakılarak
• Adenom görülmezse klinikopatolojik korelasyon gerektirir
  • Hâlâ sellada adenom var mı?
  • Kortikoid yüksekliğinin başka nedenleri
  • Aspiratörde ya da seri kesitlerde kaybolan adenom?

ACTH Crooke değişiklik yok, adenom yok

• Kortikotrop hiperplazi?
  • Patolojik değerlendirme zor olabilir
• Psödo Cushing

ACTH – Crooke cell adenoma

Adenomatöz hücrelerin sitoplazmasında yoğun birikim

Nükleer pleomorfizm, iri hücre

DDX: gangliositom, metastaz

ACTH +

Yoğun halka şeklinde keratin birikimi

CAM 5.2 +

p53

Ki-67

Pit-1

ER-α

Mukozada ekilim?

Serum – IHK korelasyonu

Otopside inceleme

Stalk yüksekten kesilmeli

Sella kontrol edilmeli

Dorsum sella dan açılarak intakt çıkartılmaya çalışılmalı

Alıntı slaytlar

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Adenohipofiz

Lateral kanat

Mukoid wedge

Hipofiz adenomu sınıflandırması

Cerrahi, radyoloji

• İnvazif
  • Dura
  • Kemik
  • Sinüsler
• Non-invazif

Hormon aktif

Nonfonksiyone

Mikroadenom <1cm

Makroadenom >1cm

Büyüme Hormonu Adenomu

%10

%25-30

Gigantizm, akromegali

İnvaziv makroadenom

IGF-1

Yoğun granüllü GH adenomu

Yuvarlak, polihedral, asidofilik

Yaygın, kuvvetli sitoplazmik GH

Perinükleer CK8

Yarısında α-subünit pozitif

Pit-1 kuvvetli nükleer pozitif

EM sekretuvar granüller bol

Seyrek granüllü GH adenomu

• Küçük, yuvarlak, kısmen düzensiz hücreler

• Fibröz cisimler

  • Paranükleer soluk asidofilik küresel inklüzyon
  • LMWCK, CK8 pozitif

• Pleomorfizm, çok çekirdekli bizar hücreler

• GH zayıf sitoplazmik

• Pit-1 kuvvetli nükleer pozitif

• Daha agresif

• Multinükleer, pleomorfizm

  • Prognostik değil

• Makroadenom, invazif

• Otokrin

  • GHrH salgılıyor

PRL hücre adenomu

• %25-30
• Serum PRL düzeyi genelde tümör boyutu ile paralel
  • >150ng/mL tanısal
  • Daha düşük değerler bası etkisini yansıtır
• Kadınlarda mikroadenom şeklinde
  • Galaktore, amenore
• Erkeklerde
  • Libido azalması, impotans
• Mikroadenom lateral ve posteriorda
• Genelde diffüz, nadiren papiller
• Nadir iri, uzun hücreler, belirgin membran

Amiloid depolanması, kalsifikasyon

Pitüiter taş

Seyrek granüllü laktotrop adenomu

• Kromofob, amfofilik
  • *Belirgin ** *rough __ endoplazmik retikulum içerir__
• Paranükleer (golgi) paterninde PRL pozitif
• Pit-1 nükleer kuvvetli

Yoğun granüllü laktotrop adenomu

Nadir

Dopamin agonisti tedavisi etkisi

Atrofi

Hücre boyutunda küçülme

Sitoplazmada büzüşme

N/C oranında artma

İnterstisyel ve perivasküler fibrozis

TSH hücre adenomu

Nadir

İnvaziv

Solid, sinüzoidal patern

Stromal fibrozis, psammom cisimleri

Hücre sınırları belirsiz kromofob adenom

Nükleer pleomorfizm olabilir

PAS sitoplazmik granüller

Sitoplazma: α-subünit, β-TSH

Nükleer Pit-1

Plurihormonal ekspresyon izlenebilir

ACTH hücre adenomu

• %10-15
• Makroskopik: kırmızı ve yumuşak mikroadenom
• Seri kesitlere rağmen izlenemeyebilir
• Nadir kavernöz sinüs invazyonu
  • Klinik ve biyokimyasal semptom yok
  • Sessiz

Diffüz, sinüzoidal

Bazofilik, amfofilik, monomorfik, yuvarlak

Kuvvetli PAS pozitif

Crooke hyalen değişim

Pleomorfizm

Mitoz nadir

ACTH, β-LPH ve/veya β-endorfin

Cushing hastalığı (pitüiter ACTH fazlalığı)

Nelson zemininde gelişen

Crooke cell adenoma

Sessiz kortikotrop adenomlar

Cushing hastalığı (pitüiter ACTH fazlalığı)

Gonadotrop hücre adenomu

Nadir?

Fonksiyonel olanlar erkeklerde daha sık

Sessiz adenomlarda IHK ile tanı konur

Makroadenom

Supra, parasellar

Sinüzoid, psödorozet

Kanama, nekroz olabilir

PAS negatif, onkositik olabilir

α-subünit, β-FSH (daha sık), β-LH pozitif

Plurihormonal Adenomlar

• Pit-1
  • Karışık somatotrop-laktotrop
    • Akromegali, stalka bası
    • İki farklı hücre tipi
  • Mammosomatotrop
    • Klinik sakin, akromegali, hiperPRL
    • Aynı hücrede GH ve PRL
  • Asidofil kök hücre
    • Klinik sakin veya hiperPRL
    • Kromofob
    • İnvaziv
    • Paranükleer vakuol
    • Agresif seyir
  • Plurihormonal GH üreten adenomlar
    • Yoğun granüllü GH adenomu
    • PRL, α-subünit, β-TSH, β-FSH, β-LH
• ACTH-α subünit
• LH/FSH-PRL-β-endorfin
• GH-ACTH
• PRL-TSH

Null Hücre Adenomu

%20, giderek düşüyor

Suprasellar, parasellar invazyon

Kavitasyon, kanama

Yuvarlak, poligonal, kromofob

Diffüz, papiller

Pleomorfizm, mitoz nadir

İnvaziv

Kemik

Kavernöz sinüs

Nazofarenks

Dura

• Agresif davranış
  • Rekürrens
  • Hormon düzeyi normale dönmez
• Dura invazyonu sık
  • Agresif değil

Atipik adenom

• Biyolojik
  • Agresif davranış
  • Rekürrens
• Ki-67>%3
• p53 pozitif
• Metastaz yaparlar mı?

Hipofiz karsinomu

• BOS ya da sistemik yayılımla tanı konur
• Erişkinlerde
• Nadir
• PRL, GH
• ACTH olanlar Nelson zemininde
• İnvazyon, pleomorfizm, mitoz ve nekroz izlenir
  • Ancak tanısal ya da prediktif değildir

Cadillac approach

Acta Neuropathol (2006) 111: 68–70

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Hipofiz adenomu

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